Signal Transduction by Phase Separation—Unnoticed Revolution in Molecular Biology

Abstract

Recent scientific findings highlight the crucial role of liquid-liquid phase separation (LLPS) in the compartmentalization of enzyme systems. A synthesis of the extant data indicates that lipid rafts and condensates formed by phase separation are also implicated in signal transduction, including participation in recognized receptor systems. The intrinsically disordered nature of many membrane-binding proteins, coupled with their propensity for LLPS, provides condensate formation, which can bind to or form on the membranes. Moreover, condensates can form simultaneously on both sides of the membrane at lipid raft regions facilitating signal transmission across the membrane. The finding that LLPS plays a direct role in cell signaling, especially in well-defined transmembrane signaling pathways, represents a substantial, yet largely unrecognized, advancement in understanding of intracellular signal transduction mechanisms.